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NO SURPRISE Here: Brexit causing uncertainty for clinical supply

July 27, 2017

This week's blog post will focus on the uncertainty that Brexit brings to the clinical supply field. One of our upcoming Sherpa Summer Seminarspeakers, John Shillingford, PhD, Independent Consultant, was kind enough to blog about some concerns that sponsor companies should consider as they consider holding clinical trials in the EU or the UK in 2019 (when Brexit is scheduled to be official).

If you would like to discuss Brexit's impact on clinical trials further, don't forget to sign up for the Sherpa Summer Seminar on August 10!

LOOMING BREXIT MEANS UNCERTAINTY FOR CLINICAL TRIALS IN THE UK & EU

By John Shillingford, Independent Consultant

The UK has been an uneasy member of the European Union for many years and it came as no total surprise when on the 23rd of June 2016 the UK population voted to step out of the European Union and Brexit was born.

In a burst of exultation one article [1] was published in a broadsheet indicating that the UK “will now be free of EU rules for Clinical Studies that were bureaucratically choking the Clinical Research community.” However, this so called heavy and unnecessary EU bureaucracy is no more than that required by ICH (International Committee on Harmonisation) Research Guidelines. As these are embraced around the world as the requirements to ensure patient safety and data integrity, for the UK to shake off this shackle would be simply impossible. Many false and confusing rumours have followed including a typical Ministerial statement made by a “Brexiteer MP” (Member of Parliament) that the UK “Will keep the European Medicines Agency in London.” This has since been clarified as an impossibility by the EMA itself.

European Medicines Agency (EMA) Relocation Will Cause Slowdown in the Global Clinical Research Community

Much has subsequently been written regarding the effect of Brexit to clinical research in the UK – but Brexit also has significant effects on the global research community, who now have to navigate uncharted waters. Whilst the UK Medicines and Healthcare Products Regulatory Agency (MHRA) have acknowledged that the European Medicines Agency (EMA) will be duty bound to leave the UK, this is not without enormous regret. Thomas Lönngren, former executive director of the EMA has indicated that it is almost impossible to relocate the Agency without a slowing of its procedures .[2] EMA’s move coupled with the expected relocation of many expert assessors and related staff will all happen in 2019 thus unless the planning and execution is unbelievably efficient, we must expect a period of frustration whilst the systems are re-established. Many countries are currently showing interest in hosting the EMA with Budapest, Barcelona, Paris and Berlin certainly throwing their hats into the ring. The EMA has initiated twoworking groups ,[3] one for Pharmaceuticals and one for Veterinarian products to look at all aspects of Brexit and recommend how to proceed. Clearly it is in the Interests of all parties, Political, Medical and Industrial, to ensure a smooth transition is made to whatever the next steps are.

Does Brexit Mean Exit from the 2019 One Portal Clinical Trial Assessment and Approval System?

Experts in the MHRA have been very active in the formulating of the new EU Legislation which is bringing in the new one portal clinical trial assessment and approval system in 2019.[4],[5] EU Regulation 536/2014 will harmonize the assessment and supervision processes for clinical trials throughout the EU, via an EU portal and database. The EMA will set up and maintain the portal and database, in collaboration with the member states and the European Commission. As Britain enters the Brexit negotiations, it is feared that access to this system is at risk, despite the fact the MHRA have been fundamentally involved in the framing of the legislation to bring this into effect. Non-access will reduce the attractiveness of the UK as this will necessitate a separate submission outside of the one portal system, which may be viewed as an unnecessary extra cost, given the relatively small size of the UK marketplace.

The MHRA role in driving through the new EU Medical Device Regulations, due to come into force later this year is again an indicator of just much the UK has influenced health care research in Europe. It can only be hoped that as Brexit negotiations progress, the political classes do not damage these professional relationships with UK patients becoming the poorer because of political expediency.

Brexit’s Effects on the Role of the Qualified Person (QP)

The UK has been a popular route for non-EU countries (i.e. US) for entry into the EU for Clinical Trial Investigative Products, which need the approval of a QP for entry into the EU for clinical trial purposes. The EMA has also indicated in a Questions and Answer paper [6],[7] issued in May 2017 that as of the date of withdrawal from the Union, active substances manufactured in the UK will be considered as “imported” active substances for the EU. Clearly this will mean that Medicinal products that have in the past been imported into the EU via the UK will now have the hurdle to meet the EU Directives for Manufacturing standards performed by a Qualified Person who must be based in an EU country and thus the companies involved in manufacturing, packing and distribution of not only Investigative Medicines, but also all medicines, will need to alter strategies and develop facilities in an EU base to be able to provide these services.

Indeed, to clarify this further, the EMA has clearly indicated that as far as Drug entry and distribution for both Clinical Research and Marketed products, the UK will be regarded as a “Third Country” and thus any entry of Medicinal Product into the EU member states from the UK, will be treated as such and require review, audit and approval of a QP based within an EU country. This will thus mean that any Manufacturing Unit within the UK will need Audit and approval to the EU Directives. This in itself will not be problematical as such units do already comply, but it is yet another hurdle to be crossed.

The same will be true for the Qualified Person for Pharmacovigilance Surveillance, with this function moving to an EU base. Post Brexit any MHRA eudravigilance system will need to be interactive with the EU system to ensure complete and comprehensive collection of Adverse Event (AE), Serious Adverse Event (SAE) and Suspected Unexpected Serious Adverse Reaction (SUSAR) data and thus ensure patient safety. One can only hope that sense prevails and direct interaction with the EU system is maintained. A recent contributor at a Pharmacovigilance Conference – (Vicki Edwards) May 2017, suggested that the PV QP has (as things now stand in the Brexit negotiations) three choices: remain a QPPV and relocate to another country in the EU, accept an alternative UK-based position within a marketing authorisation holder (MAH), or accept redundancy.

A Fork In the Road Lies Ahead: UK or the EU?

A recent survey of clinical trial experts both in the UK and on mainline Europe indicated two differing views. The UK respondents commented that whilst they were acknowledging the issues and difficulties, the positive thinking is that in the long run, the changes that have been put in place with HRA efficiencies and presence of research study co-ordinators in Health Authority Units/Hospitals, should be enough to maintain the attractiveness of the UK for Clinical Research. This is further boosted by acknowledgement of the standing the MHRA has had in the European Healthcare community in its work with the EMA.

The European approach appears to be more cautious. Currently work that is being placed in the UK tends to be short term (Early Phase – 1 to 2b) with an associated – wait and see attitude for longer projects. Some companies have ceased to place work altogether until the Brexit issues become clearer. There is a further concern that as some 55,000 National Health Service (NHS) employees are from an EU country, and as this status of these nationals is currently unclear, then it is acknowledged that there is a potential skills shortage that may inhibit R&D projects.

Clearly the next year or so could be difficult for the Industry in the UK with uncertainty remaining the major issue. The sooner the MHRA can announce clarity of process for regulatory processes, eudravigilance and Investigative Medicinal Product (IMP) issues, the better. However, the fear remains that as the negotiations now lay in the hands of the politicians, the hope is that they will see sense and appoint negotiators from within the MHRA, who understand the huge issues at stake, both for the health care and pharmaceutical industries in the UK and ultimately of course, for the patients.

What's Next?

Clearly there are many items still up in the air concerning Brexit. As Brexit negotiations proceed, sponsor companies will need to stay up to date with the developments outlined in this blog post. In the meantime, if you're in San Diego, we encourage you to come discuss Brexit and QP Processes with us in person during our Sherpa Summer Seminar on August 10! Come for the talks, stay for the drinks and BBQ.

About The author: John Shillingford, PhD

John Shillingford, PhD is an Independent Consultant whose career in both the Pharmaceutical and CRO industries has stretched over 40 years. John has both lived and worked in a number of European Countries as well as the USA. He is now lives in Germany.

His wide experience of Drug and Medical Device Development in Europe and the USA has been acquired during the management of both Clinical and Data Operations for major Global Programmes. A major focus has been to successfully commence and manage Operations in the Countries of Central and Eastern Europe and integrate these Research Units into Global Operations.

John has held senior positions in Management, Clinical Operations and Project Management for, Aptiv Solutions, Averion International (a Medical Device Research Company), PRA International and Imform GmbH. Currently John is a researcher at the Clinical Research Foundation, a member of the Board of Orsus Medical Ltd, a UK based Medical Device Company and additionally continues to run a number of training courses.

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